Pharmacology of human experimental anxiety - scielo.br · Pharmacology of human experimental anxiety 1Departamentos de Neurologia, ... Janke W & Netter P (1983)

421

Braz J Med Biol Res 36(4) 2003

Human experimental anxiety

Pharmacology of humanexperimental anxiety

1Departamentos de Neurologia, Psiquiatria e Psicologia Médica, and2Farmacologia, Faculdade de Medicina de Ribeirão Preto,Universidade de São Paulo, Ribeirão Preto, SP, Brasil

F.G. Graeff1, A. Parente1,C.M. Del-Ben1 and

F.S. Guimarães2

Abstract

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CorrespondenceF.G. Graeff

Pós-Graduação em Saúde Mental

Departamento de Neurologia,

Psiquiatria e Psicologia Médica

FMRP, USP

Av. 9 de Julho, 980

14025-000 Ribeirão Preto, SP

Brasil

Fax: +55-16-635-0713

E-mail: [email protected]

Research supported by FAEPA,

Hospital das Clínicas, FMRP-USP

and FAPESP.

Received August 8, 2002

Accepted December 12, 2002

Key words� Anxiety� Experimental anxiety� Humans� Anxiolytic drugs� Anxiety disorders

Introduction

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Brazilian Journal of Medical and Biological Research (2003) 36: 421-432ISSN 0100-879X Review

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Aversive conditioning to tones

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Figure 1. Skin conductance responses (SCR) of healthy volunteers undergoing aversiveconditioning to tones. Points indicate the mean value of the natural log of SCR to each tone.In the group “With pairing” (filled triangles) the 11th tone was followed by noise (aversiveunconditioned stimulus) presentation. Noise was absent in the group “Without pairing”(open triangles). N = 10. Modified from Ref. 8.

Table 1. Effects of drugs on conditioned skin conductance responses.

Drug Dose Test phase Reference(mg, po)

Habituation Extinction

Diazepam 2 +a +a Hellewell et al. (9)Buspirone 5 + + Hellewell et al. (9)Fluvoxamine 25 +a +a Hellewell et al. (9)Ritanserin 10 0 + Hensman et al. (10)Nefazodone 100 0 0 Silva and Leite (11)

200 0 0d-Fenfluramine 15 0 -b Hetem et al. (12)

30 0 0mCPP 15 0 -b Connel et al. (13)

mCPP = methyl-chlorophenylpiperazine. +, facilitation (anxiolytic); -, impairment (anx-iogenic); 0, no change. ain women only; bnearly significant.

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Figure 2. Anxiolytic effect of ritanserin (10 mg, po, triangles) measured in healthy volunteersundergoing the aversive conditioning test. Other specifications are given in the legend toFigure 1. SCR = skin conductance responses. Modified from Ref. 10.

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Simulated public speaking

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Table 2. Flowchart of the experimental session in the simulated public speaking (SPS)test as in Zuardi et al. (31).

Time (h:min) Phases Measures

-0:25 Adaptation-0:10 Initial (B) VAMS, STAI-T, STAI-S, SSS, BP, HR0:00 Drug intake1:00 Pre-stress (P) VAMS, STAI-S, SSS, BP, HR1:10 Instructions1:13 Speech preparation1:15 Anticipatory anxiety (A) VAMS, STAI-S, SSS, BP, HR1:20 Onset of speech1:22 Performance anxiety (S) VAMS, STAI-S, SSS, BP, HR1:28 Resumes speech1:30 End of speech2:00 Final (F) VAMS, STAI-T, STAI-S, SSS, BP, HR

VAMS, Visual Analog Mood Scale; STAI, State (S)-Trait (T) Anxiety Inventory; SSS,Somatic Symptoms Scale; BP, arterial blood pressure; HR, heart rate.

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Table 3. Effects of drugs on simulated public speaking.

Drug Dose Test phase Reference(mg, po)

Before During After

Diazepam 5 0 0 0 McNair et al. (22)10 - - -10 0 0 0 Graeff et al. (33)a

10 - - - Guimarães et al. (34)a

10 - 0 - Zuardi et al. (31)Lorazepam 2 - - 0 Guimarães et al. (28)Flumazenil 1b 0 - 0 Kapczinski et al. (35)Metergoline 12 +c 0 0 Graeff et al. (33)a

Buspirone 5 0 0 0 Guimarães et al. (34)a

Ipsapirone 5 0 - 0 Zuardi et al. (31)Clomipramine 25 0 + 0 Guimarães et al. (28)Ritanserin 2.5 0 0 0 Guimarães et al. (36)

10 0 0 +Nefazodone 100 0 0 0 Silva et al. (18)

200 0 + 0d-Fenfluramine 15 0 0 - Hetem et al. (12)

30 0 - 0- Tryptophan - 0 +d 0 Monteiro-dos-Santos et al. (37)

- 0 0 0e Shansis et al. (38)mCPP 15 0 0 0 Connel et al. (13)Maprotiline 50 - - - Guimarães et al. (28)Cannabidiol 300 0 0 - Zuardi et al. (31)

mCPP = methyl-chlorophenylpiperazine. +, increase; -, decrease; 0, no change.aaudiocassette recorder; biv; cSpielberger’s anxiety scale; din female, but not in malesubjects; eonly male subjects in the study.

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Figure 4. Nefazodone enhances the anxiety induced by simulated public speaking. N = 15.NEF100: 100 mg, NEF200: 200 mg nefazodone. Other specifications are given in thelegend to Figure 3. Modified from Ref. 18.

Figure 3. d-Fenfluramine reduces the anxiety induced by simulated public speaking inhealthy volunteers. Points indicate mean of 15 subjects in mm of the Visual Analog MoodScale (VAMS). B: initial measurement, P: pre-stress, A: anticipatory anxiety, S: speakingperformance anxiety, F: final, post-stress measure. DF15: 15 mg, DF30: 30 mg d-fenflur-amine. *P<0.05 compared to placebo (Duncan�test). Modified from Ref. 12.

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Stroop Color-Word test

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Table 4. Effects of drugs on state anxiety in the Stroop Color-Word test.

Drug Dose (mg, po) Effect Reference

Diazepam 5 - Nakano et al. (45)5 - Leite et al. (46)

Lorazepam 0.94a 0 Tulen et al. (47)Nabilone 2 - Nakano et al. (45)

-, decrease (anxiolytic); 0, no change.acumulative dose after repeated drug administration and testing.

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Table 5. Effects of drugs on fear-potentiated startle.

Drug Dose (mg, po) Effect Reference

Diazepam 10 - Patrick et al. (52)15 -10 - Bitsios et al. (53)

Alprazolam 0.25-1 - Riba et al. (54)Ethanol Drink 0 Curtin et al. (55)

-, decrease (anxiolytic); 0, no change.

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Pharmacology of human experimental anxiety - scielo.br · Pharmacology of human experimental anxiety 1Departamentos de Neurologia, ... Janke W & Netter P (1983)